tbuckley/cabot-search huggingface dataset:
Abstract 12636: Association Between Pre-Operative Specialist Assessment and Adverse Outcomes Among Patients Scheduled for Major Vascular Surgery
Authors: Charles de Mestral, Husam M Abdel Qadir, Peter C Austin, Alice Chong, McAlister A Finlay, Thomas F Lindsay, Heather Ross, GEORGE OREOPOULOS, Duminda N Wijeysundera, Douglas S Lee
Journal: Circulation (2022)

Background: The impact of pre-operative specialist assessment on outcomes following high-risk vascular surgery remains uncertain. Our objective was to characterize the association between pre-operative cardiology or general internal medicine (GIM) assessment and post-operative outcomes following scheduled major vascular surgery. Methods: This is a population-based cohort study of all adult scheduled major vascular surgery patients in Ontario, Canada (April 1, 2004-March 31, 2019). Those who underwent an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Multivariable cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication. Results: Among 50,228 scheduled major vascular surgery patients, 20,484 underwent pre-operative ambulatory specialist assessment: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Patients who underwent cardiology or GIM assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989 [24.4%] vs. 4,587 [15.4%], p&lt;0.001) and more frequent pre-operative cardiac testing (N=7,772 [37.9%] vs. 6,113 [20.6%], p&lt;0.001) but had lower crude 30-day mortality (N=551 [2.7%] vs. 970 [3.3%], p&lt;0.001). After application of IPTW, pre-operative specialist assessment remained associated with a lower rate of 30-day mortality (Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes (Figure). Conclusion: Pre-operative ambulatory cardiology or GIM assessment is associated with improved outcomes following scheduled major vascular surgery
Abstract 11098: End-Organ Dysfunction Differs in Patients With Heart Failure-Related vs. Acute Myocardial Infarction-Related Cardiogenic Shock
Authors: Anubodh S Varshney, David Berg, Michael G Palazzolo, Erin A Bohula, Jason N Katz, Sean Van Diepen, David Morrow
Journal: Circulation (2022)

Introduction: Severity of end-organ dysfunction correlates with outcomes in acute myocardial infarction-related cardiogenic shock (AMI-CS). The epidemiology of end-organ dysfunction in heart failure-related cardiogenic shock (HF-CS) has not been well described. Methods: Cardiac intensive care unit (CICU) admissions with CS in the Critical Care Cardiology Trials Network Registry (2017-2021) were identified and categorized as AMI-CS and HF-CS ( de novo or acute-on-chronic HF). Admissions for each CS sub-type were characterized as having respiratory, kidney, liver, and/or neurologic dysfunction using definitions adapted from the Sequential Organ Failure Assessment score ( Fig A ). Outcomes were assessed by burden of non-cardiac organ dysfunction: no end-organ dysfunction (NEOD), single system end-organ dysfunction (SEOD), or multi-system end-organ dysfunction (MEOD). Results: A total of 2,911 CS admissions from 35 CICUs were identified, most of which were for HF-CS (71%, N = 2,068). The proportions of patients with NEOD, SEOD, and MEOD were 25%, 36%, 39% for HF-CS vs. 16%, 35%, 49% for AMI-CS (p&lt;0.01). NEOD, SEOD, and MEOD rates were 19%, 31%, and 49% for de novo HF-CS vs. 27%, 37%, and 36% for acute-on-chronic HF-CS (p&lt;0.01). Predominant type of organ dysfunction differed among CS sub-types, with higher rates of respiratory dysfunction in AMI-CS and de novo HF-CS (p&lt;0.01) and higher rates of hepatic dysfunction in both de novo and acute-on-chronic HF-CS (p&lt;0.01; Fig A ). In-hospital mortality was lower in acute-on-chronic HF-CS compared with de novo HF-CS or AMI-CS (25% vs. 32% vs. 38%; p&lt;0.01), with a similar gradient of risk according to burden of non-cardiac organ dysfunction (p int = 0.64; Fig B ). Conclusions: End-organ dysfunction pattern and burden differ among de novo HF-CS, acute-on-chronic HF-CS, and AMI-CS. Overall mortality is lowest in acute-on-chronic HF-CS, but mortality is similarly associated with burden of end-organ dysfunction among CS types.
Abstract 11630: Wearable Cardiac Defibrillator Use is Associated With Lower All-Cause Mortality in Patients With Ischemic Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Farzane Saeidifard, LU CHEN, Larry J Prokop, Adam S Budzikowski
Journal: Circulation (2022)

Introduction: Wearable cardiac defibrillators (WCD) have been shown to be effective for detection and treatment of ventricular tachyarrhythmias. However, their efficacy in improving survival or decreasing mortality in patients with newly diagnosed cardiomyopathy (CM) is uncertain. This study reviews the current available evidence. Method: We searched databases since inception to April 2022, without language and year of publication restriction for randomized trials and cohort studies that examined the difference between WCD use and non-use in mortality and survival among patients with ischemic and non-ischemic CM. Two independent investigators screened the abstracts and full texts and extracted the data. Data was analyzed using random effect model. Results: From 603 records identified by a librarian, only 4 randomized trials on WCD use in ischemic CM met the inclusion criteria. One of them was an abstract without any full text published. The total participants were 18,779 of which 2,408 were in the WCD group (mean age 65.12±11.5, 20.7% female) and the rest in control group (mean age 65.45±11.36, 28% female). The adjusted all-cause mortality at 3 months follow up was significantly lower in WCD group (RR 0.32, CI [0.11-0.97], including three studies, 2,360 patients in WCD group and 4,954 in control group) (heterogeneity score I 2 =86%)(figure). Adjusted all-cause mortality at 12 months was also significantly lower in WCD group (RR 0.43, CI [0.25-0.71], two studies, 857 patients in WCD group and 15,566 in control group) (heterogeneity score, I 2 =49%). Only one study reported adjusted risk for arrhythmic death, myocardial infarction, arrhythmia (atrial or ventricular), stroke and hospitalization. In addition, one study reported the difference in cost and healthcare use between the two groups. Conclusion: Our meta-analysis confirms significant reduction in all-cause mortality associated with WCD use in patients with newly diagnosed ischemic cardiomyopathy.
Abstract 11606: The Association Between Sarcoidosis and In-Hospital Outcomes Among African Americans With Acute Myocardial Infarction
Authors: Demilade A Soji-Ayoade, Kelechi O Weze, Olayiwola A Bolaji, Melvin Echols
Journal: Circulation (2022)

Introduction: Sarcoidosis (SD) has a higher prevalence among African Americans (AA). It is also associated with an increased risk of ischemic heart disease (IHD); however little is known of its effect on in-hospital outcomes after an acute myocardial infarction (AMI). Therefore, we sought to evaluate the association between SD and in-hospital outcomes among AA patients (pts). Methods: Using the National Inpatient Sample between 2005-2014, we evaluated admissions of AA presenting with AMI and a concurrent diagnosis of SD. We used propensity score matching in 1:3 fashion to create a comparison group of patients without SD based on age and comorbidities. Our primary outcome of interest was in-hospital mortality. Secondary outcomes were length of hospital stay and total cost of hospitalization. Results: We evaluated 416, 209 representative admissions of AA with AMI. Of these, we compared 2,647 had a concurrent diagnosis of SD to 7,942 pts without SD. The pt group with SD had mean age 58.1 years and were 61.5% female. When compared with the pts without SD, the pts with sarcoid were more likely to smoke (21.5% vs 19.5%, p=0.028), have liver failure (4.5% vs. 3.4%, p=0.007) and have a cancer diagnosis (2.8% vs. 2.1%, p=0.37), but less likely to have renal failure (25.0% vs 29.1%, p&lt;0.001). When compared with the pts without SD, pts with SD had a significantly lower in-hospital mortality and cost of hospitalization ($46,593±69,981 vs $51,941±80,624, p=0.023). Conclusion: Although sarcoidosis is associated with increased risk of IHD, SD is associated with lower in-hospital mortality and lower cost of care in AA pts presenting with AMI. Further investigations are warranted to understand these outcomes. Table 1: Baseline characteristics of AA patients with AMI and sarcoidosis compared with a propensity-score matched cohort without sarcoidosis.
Abstract 12047: miR-148-3p:mdfic Pathway Improves the Efficacy of Therapeutic Cardiac Reprogramming
Authors: Hualing Sun, Richard E Pratt, victor dzau, Conrad Hodgkinson
Journal: Circulation (2022)

We, and others, have demonstrated that directly reprogramming scar fibroblasts into new cardiomyocytes improves cardiac function in the infarcted heart. A major challenge is the relatively low conversion rate of fibroblasts into cardiomyocytes. We pioneered reprogramming method based on miRNAs, whereby fibroblasts were converted into cardiomyocytes via combination of four miRNAs which we called miR combo. We hypothesized that the efficacy of miR combo could be improved via additional miRNAs. To that end, we screened a number of miRNAs and found that miR-148-3p significantly enhanced the efficacy of miR combo with respect to the expression of cardiomyocyte genes (Actn2, Myh6 and Tnni3; 2 to 5 fold; N=5; P&lt;0.05). Validating a role for miR-148a-3p, addition of the anti-miR-148a-3p inhibited the ability of miR-148a-3p to enhance reprogramming efficacy (N=5, P&lt;0.05). In silico analysis, miR-148a-3p transfection studies, and luciferase reporter assays indicated that Pten, Pik3r3, Rock1 and Mdfic were miR-148a-3p targets. Of these targets, only the overexpression of Mdfic inhibited miR combo (N=4, P&lt;0.05). In contrast, siRNA-mediated knockdown of Mdfic enhanced miR combo efficacy (Actn2, Myh6 and Tnni3; 2 to 10 fold; N=3; P&lt;0.05). These studies suggested that Mdfic was a repressor of the cardiomyocyte phenotype. To provide further evidence, Mdfic mRNA levels were measured in freshly isolated cardiomyocytes and fibroblasts. Mdfic was found to be virtually absent in cardiomyocytes and strongly expressed in fibroblasts (N=3, P&lt;0.05). Moreover, ChIP-qPCR and co-immunoprecipitation analysis indicated that in fibroblasts, Mdfic resided solely on cardiomyocyte genes where it inhibited gene expression by preventing the binding of transcription activator proteins (N=3, P&lt;0.05). In summary, miR-148a-3p improves the efficacy of fibroblast to cardiomyocyte reprogramming via the down-regulation of Mdfic.
Abstract 11108: Implementation of High-Sensitivity Cardiac Troponin Assays in the United States: A Report From the NCDR Chest Pain - MI Registry
Authors: Cian P McCarthy, Shuang Li, Tracy Y Wang, Inbar Raber, Yader B Sandoval, Nathaniel R Smilowitz, Jason H Wasfy, Ambarish Pandey, James A De Lemos, Michael C Kontos, Fred S Apple, Lori B Daniels, L Kristin K Newby, Allan S Jaffe, James L Januzzi
Journal: Circulation (2022)

Introduction: High-sensitivity cardiac troponin (hs-cTn) assays were first approved for use in the U.S. in 2017. They are the guideline preferred biomarker to evaluate patients with acute chest pain. Few data exist regarding implementation of hs-cTn assays in the U.S. Hypothesis: We hypothesize that use of hs-cTn assays has increased over time and that patients assessed with hs-cTn have a shorter length of stay (LOS) and similar use of cardiac testing. Methods: We examined trends in implementation of hs-cTn assays among participating hospitals in the NCDR Chest Pain MI Registry from 1/1/2019 through 9/30/2021. Excluding STEMI patients, associations between hs-cTn use, in-hospital diagnostic imaging, and patient outcomes were assessed using logistic or negative binomial regression models. Results: Among 550 participating hospitals with 251,000 patients in the registry, implementation of hs-cTn assays increased from 3.3% in Q1, 2019 to 32.6% in Q3, 2021 (P trend &lt;0.0001; Figure ). Implementation was similar by hospital size, type, and geographic location. hs-cTn use was associated with more echocardiography among patients with NSTE-ACS (82% vs. 75%; aOR: 1.43, 95% CI, 1.19-1.73) but not in low-risk chest pain. hs-cTn use was associated with decreased odds of invasive coronary angiography in low-risk patients (3.7% vs. 4.5%; aOR: 0.73, 95% CI, 0.58-0.92) but similar use in NSTE-ACS. There was no association between hs-cTn use and non-invasive stress/CTCA testing. Among NSTE-ACS patients, hs-cTn use was not associated with PCI, CABG, or in-hospital mortality. Use of hs-cTn was associated with shorter LOS (47.6 hours vs. 48 hours; IRR: 0.96, 95% CI, 0.93-0.98). Conclusions: Although implementation of hs-cTn among U.S. hospitals is increasing, most U.S hospitals continue to use less-sensitive troponin assays. hs-cTn use was associated with shorter LOS overall, greater use of echocardiography in NSTE-ACS, and lower use of invasive angiograms in low-risk patients.
Abstract 12612: Prevalence, Risk Factors and Guideline Directed Medical Therapies Among Premature Peripheral and Coronary Arterial Disease in Large Integrated Healthcare System: Houston Methodist CVD Learning Health System Registry
Authors: Safi U Khan, Yasser Sammour, Samarthkumar Thakkar, BUDHADITYA BOSE, Rakesh Gullapelli, Charlie Nicolas, Nwabunie Nwana, Shubham Lahan, Trisha Roy, Alan Lumsden, Neil S Kleiman, Ahmed Soliman, Kershaw Patel, Miguel Cainzos Achirica, Julia Andrieni, Stephen Jones, William A Zoghbi, Khurram Nasir
Journal: Circulation (2022)

Introduction: Premature coronary artery disease (CAD) and peripheral arterial disease (PAD) are manifestations of accelerated atherothrombotic disease and pose a significant risk for CVD morbidity and mortality. There are scarce insights on prevalence, risk factors, and management practices for these high-risk groups. Methods: In this cross-sectional study, we analyzed patients aged 18-64 y in the Houston Methodist Cardiovascular Disease Learning Health System Registry (n= 1.127 million; June 2016-April 2022). CAD and PAD were identified using ICD 10-CM codes. Results: Among 811,097 individuals (58.6% women and 14.8% NH Blacks, Table ), 2.1% (n=17,094) had premature CAD alone, 0.4% (n=3,243) had isolated premature PAD and 0.2% (n=1,658) had both. Compared to premature CAD alone, patients with isolated premature PAD were more likely to be women, NH Blacks, smokers, and diabetics, with the highest risk burden seen in those with both conditions. Patients with isolated premature PAD had the lowest rates of lipids, HBA1c, and SBP at goals and guideline-directed medical therapies (GDMT) compared to those with premature isolated CAD. Conclusions: Nearly 1 in 40 adults had premature CAD and PAD. Individuals with premature PAD have a more unfavorable CV risk profile and are less likely to achieve risk factor control and receive GDMT. Therefore, system-wide collaborative initiatives for early identification and risk factor optimization for this vulnerable population are warranted.
Abstract 11998: ADAR1 Mediates Macrophage Activation by Its Non-Editing Activity-Mediated Pri-miRNA Processing in Abdominal Aortic Aneurysm
Authors: Dunpeng Cai, Sun Chenming, Takashi Murashita, Xingyi Que, Shiyou Chen
Journal: Circulation (2022)

Introduction: Macrophage activation plays a critical role in abdominal aortic aneurysm (AAA) development. However, molecular mechanisms controlling macrophage activation in AAA remain largely unknown. The objective of the study was to identify novel mechanisms underlying adenosine deaminase acting on RNA (ADAR1) function in macrophage activation and AAA formation. Methods: Aortic transplantation was conducted to determine the importance of non-vascular ADAR1 in AAA development. Angiotensin II (Ang II) infusion of ApoE–/– mouse combined with macrophage-specific knockout of ADAR1 was used to study ADAR1 macrophage-specific role in AAA formation. Primary cultured bone-marrow derived and peritoneal macrophages were used to study how ADAR1 regulates macrophage activation. Moreover, a novel humanized AAA model was established by transplanting human artery to immunodeficient mouse aorta followed by immunity reconstitution with ADAR1-deficient human monocytes to test the role of human macrophages in aneurysm formation in human arteries. Results: Allograft transplantation of wild type abdominal aortas to ADAR1+/- recipient mice significantly attenuated AAA formation, suggesting that non-vascular ADAR1 is essential for AAA development. ADAR1 deficiency in hematopoietic cells decreased the prevalence of AAA while inhibited macrophage infiltration and aorta wall inflammation. ADAR1 deletion blocked the classic macrophage activation, diminished NF-κB signaling, and enhanced the expression of many anti-inflammatory miRNAs. Mechanistically, ADAR1 interacted with Drosha to promote its degradation, which attenuated Drosha-DGCR8 interaction, and consequently inhibited pri- to pre-miRNA processing of miRNAs targeting IKKβ, resulting in an increased IKKβ expression and enhanced NF-κB signaling. Reconstitution of ADAR1-deficient, but not the wild type, human monocytes to immunodeficient mice blocked the aneurysm formation in transplanted human arteries. Conclusions: Macrophage ADAR1 promotes AAA formation in both mouse and human arteries through a novel mechanism, i.e., Drosha protein degradation, which inhibits the processing of miRNAs targeting NF-kB signaling and thus elicits macrophage-mediated vascular inflammation.
Abstract 12553: Adverse Cardiovascular Outcomes in Heart Failure (HF) With Preserved Systolic Function Associated With Atrial Fibrillation Are Due to Loss of Rhythm Control Impacting HF Status : A Propensity Score Matched Analysis of the TOPCAT Americas Study
Authors: Sanjeev Saksena, April Slee
Journal: Circulation (2022)

Background: Atrial fibrillation (AF) is associated with excess mortality and cardiovascular (CV) hospitalizations in HF patients (pts) with preserved systolic function (pEF), Whether this is due to advanced co-morbidities or loss of atrioventricular (AV) synchrony &amp; rate control in AF is unclear. Hypothesis: To analyze the independent impact of AF on clinical outcomes of HFpEF pts in the TOPCAT AMERICAS study using propensity score matched (PSM) cohorts to account for confounding by other comorbidities. Methods: Study cohorts were matched for 20 clinical, demographic &amp; ECG variables. 3 matched cohorts based on baseline rhythm status at study entry were compared viz. subjects in sinus rhythm (SR), subjects in AF on baseline ECG &amp; subjects with Any AF event by history or ECG. We analyzed CV mortality, adjudicated modes of death &amp; morbidity during a mean follow up period of 2.9 yrs. Results: 418 subjects in SR (SR cohort) were PSM with 418 subjects in AF on baseline ECG (AF on ECG cohort) &amp; 418 pts with any AF event by history or ECG (Any AF cohort) at study entry. Any AF increased risk of CV death(D), pump failure death (PFD), CV and HF hospitalization(H) and HF progression. AF on ECG increased risk of CVD, CVH, HFH and PFD (Tables). Neither AF cohort increased risk of sudden death (SD) {Figure}. Conclusion: 1. AF is an independent risk factor for worsening CV outcomes in HFpEF. 2. This increased risk is due to a selective increase in HF worsening, HFH and PFD rather than SD. 3. Loss of AV synchrony &amp; rate control in AF can independently impact HF progression in HFpEF with consequent HFH and PFD. Restoration of SR may offer benefits for CV outcomes in HFpEF &amp; warrants evaluation.
Abstract 11490: The Role of Breast Milk Extracellular Vesicles on Endothelial Dysfunction
Authors: Young-Eun Cho, Shaoshuai Chen, Keith Crouch, Jeonga Kim
Journal: Circulation (2022)

Introduction: Breast milk has abundant extracellular vesicles (EVs), which have strong anti-inflammatory properties. EVs are not degraded in the stomach, thus, orally administered milk exosomes are absorbed into the intestine and then disseminated to other organs via circulation. Circulating milk EVs in the blood have a high chance of interacting with endothelium, however, the impact of milk exosomes on the endothelial cells has not been examined. Endothelial dysfunction is a hallmark of cardiovascular diseases induced by the inflammatory process. In this study, we have tested if orally administered human breast milk EVs (bEVs) can improve endothelial dysfunction in obese mice. Hypothesis: Oral administration of bEVs restores the endothelial function in high fat diet-induced obese mice Methods: Breast milk was obtained from healthy mothers with normal pre-pregnancy BMI who delivered a baby within the past 30 days (n=24). bEVs were isolated by ultracentrifugation, and the presence of exosomes was confirmed with the expression of CD9, CD81, CD63, and TSG101. C57BL/6J male mice were fed a 60% high-fat diet for 16 weeks, then bEVs were administered weekly via oral gavage for six weeks (3μg of EVs/g). The same amount of PBS was administered to obese and chow diet-fed mice. Glucose tolerance test and insulin tolerance test were performed before and after treatment. Endothelial cell-dependent vasorelaxation was measured in the 1 st branches of mesenteric arteries. Results: Oral administration of bEVs for 6-weeks did not change body weight in obese mice. Glucose tolerance and insulin tolerance were not also affected. However, the fasting blood glucose level was significantly reduced (p=0.0012, n=5-7) in bEV-treated obese mice. In mesenteric arteries, acetylcholine-induced relaxation was significantly improved (p&lt;0.001) in bEV-treated obese mice compared with the PBS-treated obese mice. Conclusions: Oral administration of bEVs improved the endothelial cell function in obese mice, although the metabolic parameters were not changed. Further investigation will be followed to understand how bEVs improve the impaired endothelial cell-dependent vasorelaxation.